This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent advances in HCV research has resulted in the development of in vitro tissuelcell culture methodologies for the replication of HCV. It is not clear whether all of the in vitro derived HCV isolates retain their infectivity and disease causing ability. The proposed studies will determine whether certain in vitro derived isolates of HCV are infectious and cause pathogenesis in the chimpanzee model. One to two animals at a time will be injected with a particular isolate of HCV and will be monitored for evidence of infection by PCR analysis using plasma samples. If there is evidence of infection then additional blood and liver biopsy samples will be obtained for virological and immunological assays. If there is no evidence of infection, then the animals will be injected with a higher dose of the same isolate or a different isolate and monitored for infection as described earlier. Pedigreed and well characterized stocks of HCV genotype 1 and 2 virus tocks are essential to test antivial activity of new drugs that are being developed for treating HCV infected humans. In addition, the stock virus preparations can be used to determine the efficacy of candidate vaccines that are being developed for prevention of HCV infection.